Format

Send to

Choose Destination
Cancer Med. 2018 Nov;7(11):5589-5603. doi: 10.1002/cam4.1771. Epub 2018 Sep 17.

An Aurora kinase inhibitor, AMG900, inhibits glioblastoma cell proliferation by disrupting mitotic progression.

Author information

1
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea.
2
Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon, Korea.
3
Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, Korea.

Abstract

The Aurora kinase family of serine/threonine protein kinases comprises Aurora A, B, and C and plays an important role in mitotic progression. Several inhibitors of Aurora kinase have been developed as anti-cancer therapeutics. Here, we examined the effects of a pan-Aurora kinase inhibitor, AMG900, against glioblastoma cells. AMG900 inhibited proliferation of A172, U-87MG, and U-118MG glioblastoma cells by upregulating p53 and p21 and subsequently inducing cell cycle arrest and senescence. Abnormal cell cycle progression was triggered by dysregulated mitosis. Mitosis was prolonged due to a defect in mitotic spindle assembly. Despite the presence of an unattached kinetochore, BubR1, a component of the spindle assembly checkpoint, was not recruited. In addition, Aurora B was not recruited to central spindle at anaphase. Abnormal mitotic progression resulted in accumulation of multinuclei and micronuclei, a type of chromosome missegregation, and ultimately inhibited cell survival. Therefore, the data suggest that AMG900-mediated inhibition of Aurora kinase is a potential anti-cancer therapy for glioblastoma.

KEYWORDS:

AMG900; Aurora kinase; anti-cancer drug; glioblastoma; mitosis

PMID:
30221846
PMCID:
PMC6246935
DOI:
10.1002/cam4.1771
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center